Synthesis of chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities

Abstract

Chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones were produced by reacting malononitrile, barbituric acid, and aromatic aldehydes together with a DABCO catalyst in an aqueous one‐pot reaction. This is the first report of these compounds being synthesized with DABCO as a catalyst, which produced the compounds in yields in excess of 90%. The 2,4‐difluoro derivative (11) was novel. The structures of the synthesized compounds were elucidated by means of 1H, 13C, and 2D NMR spectroscopy. Compound 2 (2‐Cl derivative) had MBC values of <200μM against both Staphylococcus aureus and MRSA, and the 2‐nitro derivative 5 had an MBC of 191μM against the Gram–ve Escherichia coli. The synthesized compounds were also tested for their anticancer activity against a HeLa cell line, where all the compounds showed better activity (IC50 values between 129μM and 340μM) than 5‐fluorouracil, a commonly known anticancer drug.

Importance of Hybrid Catalysts toward the Synthesis of 5H-Pyrano[2,3-d]pyrimidine-2-ones/2,4-diones (Thiones)

“…Moreover, several of these compounds have also been studied as nonlinear optical materials and dyes. 17 In addition, pyrano [2,3-d]pyrimidines often show antimicrobial activity 18 with IC 50 values of 257 and 278 mM for 2chloro and 2-nitro derivatives, respectively (Figure 2, VII), cytotoxic activity against the HeLa cell line with an IC 50 of 129 mM (Figure 2, VIII), urase inhibitory activity 19 with an IC 50 value 106.29 mM (Figure 2, IX), and α-amylase and αglucosidase inhibitory activity 20 with an IC 50 value of 6.490 mM (Figure 2, X). This encourages the world's leading researchers to utilize broader catalytic applications for the development of lead molecules.…”

“…Among the four possible isomers of pyranopyrimidine, 5 H -pyrano­[2,3- d ]­pyrimidine scaffolds have been intensively investigated in recent times owing to their huge applicability, but the development of the main core is found to be more challenging due to its structural existence. Pyrano­[2,3- d ]­pyrimidine derivatives showed a wide range of biological and pharmacological activities including antitumor, , antibacterial, antimicrobial, antioxidant, antifungal, vasodilator, anti-inflamatory, antidiabetic, and cardiotonic activities. Moreover, several of these compounds have also been studied as nonlinear optical materials and dyes .…”